Abstract
Background:
Patients undergoing high dose chemotherapy and autologous stem cell transplantation (HDC/SCT) have received Filgrastim from day +1 through neutrophil engraftment as per institutional guidelines. Recombinant Flgrastim (Tbo-Filgrastim) has not been compared with Filgrastim post SCT for kinetics of engraftment after high dose chemotherapy and stem cell transplantation. Tbo-Filgrastim was introduced in April 2014 at our center and is currently used only in the inpatient setting after HDC/SCT; while the use of Filgrastim is exclusive in the outpatient setting after HDC/SCT. Currently Tbo-Filgrastim is not approved as a biosimilar in the US (only indicated for reduction in the duration of severe neutropenia in patients with non-myeloid malignancies) and does not carry an "interchangeability" designation.
Objective:
To review neutrophil and platelet engraftment data for patients who received Tbo-Filgrastim compared to patients who received Filgrastim after HDC/SCT.
Methods:
A comprehensive chart review was conducted on 34 patients from Sept 2013 to May 2015: 17 patients received Tbo-Filgrastim and 17 patients received Filgrastim after SCT. All discharge summaries and electronic medical records were reviewed for inpatient and outpatient status and engraftment data. A Wilcoxon rank sum test was conducted to compare the median time to engraftment for patients who received Tbo-Filgrastim vs. Filgrastim due to the non-parametric nature of the data. A Chi-Square test was done to compare proportions of patients that had febrile neutropenia. Subjects who did not receive Tbo-Filgrastim as an inpatient after the institution switch (n=3) were excluded from analyses.
Results:
| . | Tbo-Filgrastim (n=17) . | Filgrastim (n=17) . |
|---|---|---|
| Time period | 4/2014-5/2015 | 9/2013 -3/2014 |
| Disease Type | ||
| AL Amyloidosis | 10 (59%) | 14 (82%) |
| Myeloma | 6 (35%) | 2 (12%) |
| Lymphoma | 1 (6%) | 1 (6%) |
| Median Age, years (range) | 57 (41-72) | 54 (41-68) |
| Male | 11 (65%) | 10 (59%) |
| Female | 6 (35%) | 7 (41%) |
| Mobilization Regimen | ||
| G-CSF | 7 (41%) | 13 (76%) |
| Chemo + GCSF | 3 (18%) | 1 (6%) |
| G-CSF + Plerixafor | 6 (35%) | 2 (12%) |
| Preparative Regimen | ||
| Melphalan @ 200mg/m2 | 10 (59%) | 13 (76%) |
| Melphalan @ 140mg/m2 | 6 (35%) | 3 (18%) |
| CBV | 1 (6%) | 1 (6%) |
| Median number of stem cell collection; 106 CD 34+/kg (range) | 13.9 (1.8- 21.8) | 9.1 (3.9- 16.6) |
| Median number of stem cells reinfusion; 106 CD 34+/kg (range) | 8.4 (3.0-17.4) | 6.9 (3.5-10.5) |
| Febrile Neutropenia | 10 (59%) | 8 (47%) p value=0.73 |
| Median days to neutrophil engraftment (range) | 11 (9-14) | 10 (8-15) p value=0.07 |
| Median days to platelet engraftment (range) | 12 (10-21) | 12 (9-27) p value=0.49 |
| Median days of growth factor, (range) | 6 (3-10) | 10 (8-15) |
| Death | 0 | 1 |
| . | Tbo-Filgrastim (n=17) . | Filgrastim (n=17) . |
|---|---|---|
| Time period | 4/2014-5/2015 | 9/2013 -3/2014 |
| Disease Type | ||
| AL Amyloidosis | 10 (59%) | 14 (82%) |
| Myeloma | 6 (35%) | 2 (12%) |
| Lymphoma | 1 (6%) | 1 (6%) |
| Median Age, years (range) | 57 (41-72) | 54 (41-68) |
| Male | 11 (65%) | 10 (59%) |
| Female | 6 (35%) | 7 (41%) |
| Mobilization Regimen | ||
| G-CSF | 7 (41%) | 13 (76%) |
| Chemo + GCSF | 3 (18%) | 1 (6%) |
| G-CSF + Plerixafor | 6 (35%) | 2 (12%) |
| Preparative Regimen | ||
| Melphalan @ 200mg/m2 | 10 (59%) | 13 (76%) |
| Melphalan @ 140mg/m2 | 6 (35%) | 3 (18%) |
| CBV | 1 (6%) | 1 (6%) |
| Median number of stem cell collection; 106 CD 34+/kg (range) | 13.9 (1.8- 21.8) | 9.1 (3.9- 16.6) |
| Median number of stem cells reinfusion; 106 CD 34+/kg (range) | 8.4 (3.0-17.4) | 6.9 (3.5-10.5) |
| Febrile Neutropenia | 10 (59%) | 8 (47%) p value=0.73 |
| Median days to neutrophil engraftment (range) | 11 (9-14) | 10 (8-15) p value=0.07 |
| Median days to platelet engraftment (range) | 12 (10-21) | 12 (9-27) p value=0.49 |
| Median days of growth factor, (range) | 6 (3-10) | 10 (8-15) |
| Death | 0 | 1 |
Conclusions:
In this retrospective chart review, we did not find any significant difference in time to neutrophil engraftment after HDC/SCT when comparing patients who received Filgrastim and then switched to Tbo-Filgrastim after SCT. Even though Tbo-Filgrastim is not approved as a biosimilar and lacks interchangeability designation, based on our experience the safety, efficacy and immunogenicity is comparable to Filgrastim and there are no clinical meaningful differences between the two products. However, this data warrants further prospective research with a larger sample size to confirm these findings.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
